ZNF750 represses breast cancer invasion via epigenetic control of prometastatic genes
ZNF750 represses breast cancer invasion via epigenetic control of prometastatic genes
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DOI：
10.1038/s41388-020-1277-5
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发表时间：
2020-04-20
期刊：
影响因子：
8
通讯作者：
Melino, Gerry
中科院分区：
文献类型：
--
作者：
Cassandri, Matteo;Butera, Alessio;Melino, Gerry
乳腺癌是妇女癌症相关死亡的第二大原因，主要是由于很大一部分原发肿瘤进展到转移阶段。在这里，我们发现锌指蛋白750 （ZNF750）通过抑制一个前转移性转录程序来反对乳腺癌细胞的迁移和侵袭，该程序包括参与局灶黏附和细胞外基质相互作用的基因，如LAMB3和CTNNAL1。在机制上，ZNF750将表观遗传修饰因子KDM1A和HDAC1招募到LAMB3和CTNNAL1的启动子区域，影响组蛋白标记并激活这些基因组位点。癌症患者数据集的基因表达分析表明，ZNF750及其靶点是乳腺癌的负面预后因素。总之，我们的发现揭示了ZNF750调节细胞迁移和侵袭的分子机制，提示在乳腺癌转移中起作用。
Breast cancer is the second leading cause of cancer-related deaths among women, largely due to the progression of a significant fraction of primary tumours to the metastatic stage. Here, we show that zinc-finger protein 750 (ZNF750) opposes the migration and invasion of breast cancer cells by repressing a prometastatic transcriptional programme, which includes genes involved in focal adhesion and extracellular matrix interactions, such as LAMB3 and CTNNAL1. Mechanistically, ZNF750 recruits the epigenetic modifiers KDM1A and HDAC1 to the promoter regions of LAMB3 and CTNNAL1, influencing histone marks and transactivating these genomic sites. Gene expression analysis in cancer patient datasets indicated that ZNF750 and its targets were negative prognostic factors in breast cancer. Together, our findings shed light on the molecular mechanism by which ZNF750 regulates cell migration and invasion, suggesting a role in breast cancer metastasis.